Vascular
General information
- Cerebral vein thrombosis
- Localised outflow obstruction and oedema
- Venous infarction and petechial haemorrhages
- Vasogenic oedema and cytotoxic oedema
- Venous sinus thrombosis
- Venous outflow obstruction and arachnoid granulation obstruction
- Widespread oedema and failure to resorb CSF
- Intracranial hypertension
Numbers
- Comprises 0.5% to 3% of strokes
- More common in young people
- 78% occur in patients age <50 years
- 3:1, F:M
- Incidence:
- 1.32 per 100,000 person years,
- Higher incidence in women 31–50 years of age: 2.78/100,000 person years
- Patients are usually either mildly symptomatic or extremely ill and unstable.
There are 3 types of CVT which may produce venous infarctions:
- Dural sinus thrombosis (DST)
- Cortical venous thrombosis
- Deep venous thrombosis
Aetiologies
Condition | Prevalence (%) | Trigger Type |
Prothrombotic conditions | 34.1 | Chronic |
Pregnancy and puerperium | 21.0 | Transient |
Oral contraceptives/hormone replacement | 54.3 | Transient |
Drugs (eg, danazol, lithium, vitamin A, IV immunoglobulin, ecstasy) | 7.5 | Transient |
Cancer related - Local compression - Hypercoagulability - Antineoplastic drugs (eg, tamoxifen, L-asparaginase) | 7.4 | Transient or chronic |
Infection - Parameningeal (eg, ear, sinus, mouth, face, and neck) - Sepsis | 12.3 | Transient |
Mechanical precipitants - Complication of epidural blood patch - Spontaneous intracranial hypotension - Lumbar puncture | 4.5 | Transient |
Dehydration | No prevalence data but is a recognized trigger | Transient |
Other hematologic disorders - Paroxysmal nocturnal hemoglobinuria - Iron deficiency anemia - Thrombocytopenia - Nephrotic syndrome - Polycythemia | 12.0 | Chronic |
Systemic diseases - Systemic lupus erythematosus - Behçet disease - Inflammatory bowel disease - Thyroid disease - Sarcoidosis - Other | 7.2 1.0 1.0 1.6 1.7 0.2 1.7 | Chronic |
None identified | 12.5 | Unknown |
- Infection
- Usually local
- Otitis media
- Leading to the now obsolete term otitic hydrocephalus
- Mastoiditis can lead to lateral (transverse) sinus thrombosis
- Sinusitis
- Peritonsillar abscess
- Paranasal sinusitis
- Meningitis
- Pregnancy & puerperium:
- Highest risk at
- 3rd trimenster and
- 6–8 weeks post-partum.
- Incidence ≈ 1/10,000 births.
- Due to
- Elevation of clotting factors (VII, X, and especially factor VIII).
- Hypercoagulability increases post-partum due to volume depletion and trauma.
- Oral contraceptives (birth control pills (BCP)
- Dehydration and cachexia (marantic thrombosis):
- Includes burns and cachexia of neoplastic disease
- Cardiac disease (including CHF)
- Ulcerative colitis (UC):
- 1% of UC patients have some thrombotic complication (not necessarily all intracranial)
- Thrombosis causes ≈ 33% of deaths (usually pulmonary embolism, PE)
- Periarteritis nodosa
- Sickle cell trait
- Trauma: including closed head injury
- A rare sequelae of closed head injury.
- CVT occurs in ≈ 10% of combat injuries involving the brain.
- May occur in absence of skull fracture.
- CVT should be suspected in patients with fractures or missiles crossing sinus.
- Iatrogenic:
- Radical neck surgery,
- Transvenous pacemaker placement,
- Post-craniotomy,
- Internal jugular vein catheterization
- Malignancy: including myeloproliferative disorders
- Hypercoagulable state (AKA thrombophilia or prothrombotic conditions)
- Protein C deficiency or resistance to activated protein C:
- Hereditary factor V Leiden mutation may produce resistance to activated protein C.
- Apparent protein C deficiency may be an artifact ofdehydration in some cases
- Antithrombin III deficiency
- Protein S deficiency
- Antiphospholipid antibodies:
- Associated with a variety of clinical syndromes including ischemic stroke, DVTs, thrombocytopenia, and systemic lupus erythematosus (SLE).
- Best known antibodies include
- Anticardiolipin antibodies
- Lupus anticoagulant
- Paroxysmal nocturnal hemoglobinuria (PNH)
- Plasminogen deficiency
- Prothrombin G20210A mutation of factor II:
- Causes a mild elevation of prothrombin
- Systemic lupus erythematosus
- Factor VIII elevation: may explain some cases of CVT in pregnancy)
- Diabetes mellitus: especially with ketoacidosis
- (Hyper) homocystinuria
- Behçet’s syndrome
- Rarely associated with lumbar puncture, associated with hereditary activated protein C resistance due to the factor V R506Qmutation (FV Leiden) in one report
Relative frequency of venous structures involved (think 3D remember)
- Sinuses
- Superior sagittal sinus (SSS): 70%
- Left transverse sinus (TS): 70%
- Multiple sinuses in 71%
- Isolated inferior sagittal sinus: rare
- Straight sinus
- Superficial cortical veins
- Deep venous system (e.g. internal cerebral vein)
- Cavernous sinus:
- Rare
- Thrombophlebitis of the cavernous sinus may be caused by sphenoid sinusitis.
- MRI may show
- Enlargement and abnormal enhancement of the cavernous sinus,
- Increased signal of the petrous apex and clivus on T2WI
- Narrowing of the cavernous portion of the ICA
Pathophysiology
- Venous thrombosis -->
- Reduces venous outflow from the brain -->
- If in SSS can lead to reduce CSF reabsorption --> HCP--> raised intracranial pressure
- Diminishes effective blood flow to the involved area -->
- Venous engorgement --> venous stasis
- White matter edema
- Infarction (venous infarction) --> hemorrhage
- These processes may all elevate ICP.
- Thus clinical findings due to
- Global findings: Elevated ICP,
- Focal findings: edema and/or hemorrhage.
Clinical presentation
- Fq (ferro et al 2004)
- Headache 90%
- Headache alone 15%
- Papilledema 30%
- Confusion 20%
- Speech deficit - 20%
- Weakness - 40%
- Seizures - 40%
- Coma - 15%
- No pathognomonic findings.
- Many signs and symptoms are due to elevated ICP as a result of impaired venous outflow and may present as a syndrome clinically indistinguishable from idiopathic intracranial hypertension
- There is a high association of concurrent thromboembolic disease in other organs.
- Cavernous sinus
- Painful ophthalmoplegia,
- Proptosis
- Chemosis
- Oedema of periorbital structures.
- Facial numbness and fevers.
- Superior sagittal sinus (SSS)
- Anterior 1/3: May occlude without neurologic sequelae.
- Posterior to this (especially posterior to the vein of Trolard), venous infarction --> symptoms is more likely to develop
- Mid SSS occlusion → increased muscle tone ranging from spastic hemi- or quadriparesis to decerebration.
- Posterior SSS thrombosis → field cuts or cortical blindness, or massive stroke with cerebral edema and death.
- SSS occlusion alone will not cause cranial nerve findings except perhaps for visual obscuration and abducens (VI) nerve palsy from elevated ICP.
- Transverse sinus
- Occlusion may occur without deficit unless the contralateral TS is hypoplastic
- If so then presentation is similar to posterior SSS occlusion.
- Jugular bulb
- Thrombosis may compress the nerves in the jugular foramen pars nervosa causing
- Hoarseness, aphonia, difficulty swallowing and breathlessness
- Vernet’s syndrome
- Paralysis of the IX, X, and XI cranial nerves traversing the jugular foramen.
Site of venous thrombosis | Clinical features |
Superior sagittal sinus | Headache and raised ICP Motor deficits, hemorrhagic infarction Seizures Scalp edema, dilated scalp veins |
Transverse (lateral) sinus | Signs of cause (otitis media, mastoiditis, ear discharge) Fever and systemic features Hemianopia, contralateral weakness, aphasia, |
Cavernous sinus | Orbital pain, chemosis, and proptosis Cranial nerve palsy (III, IV, VI, V1) |
Deep venous system (ICV, VoG, straight sinus) | Thalamic or basal ganglia infarction Rapid neurological deterioration |
Diagnosis of dural sinus thrombosis, DST
General information
- CT (especially CTV) & MRI/MRV are very sensitive and specific for identifying areas of clot.
- Catheter angiography is better at demonstrating the presence of residual flow, and can identify areas of reversal of flow, and sometimes is able to demonstrate clot as a filling defect.
- Angiography is often used as a complementary test when the diagnosis is suggested by CT or MRI.
CT scan
- Non-contrast CT Low sensitivity.
- A wide range of accuracy is reported:
- 30–100% sensitivity &
- A realistic range of sensitivity from reviews is ≈ 30% to 75% of cases of CVT
- 83–100% specificity
- Hounsfield unit (p.243) > 70 is highly specific for acute CVT.
- False positives may occur with high hematocrit.
- Findings on noncontrast computed tomography include:
- Hyperdense sinus or cortical vein (aka Cord sign):
- Due to high density clots in cortical veins;
- Pathognomonic for cerebral venous thrombosis;
- Seen in only 2/30 patients
- Hemorrhage:
- 9–39% show some form of hemorrhage
- Petechial “flame” hemorrhages (intraparenchymal):
- Seen in 20%
- Suspect sinus thrombosis with intracerebral hemorrhages in unusual locations for
- Aneurysm or
- Hypertensive hemorrhage
- SAH:
- In <1%
- Usually over convexity
- Intraventricular
- Small ventricles: seen in 50%
- Thrombosis of superior sagittal sinus
- May produce a triangular-shaped high density within the sinus posteriorly near the Torcular herophili on axial CT images (delta sign or “dense/filled delta sign” as opposed to the “empty delta” sign)
- There is also confusion when an apparent “empty delta” sign is seen without contrast; this may occur when there is blood surrounding the SSS, e.g. following subarachnoid haemorrhage; this has been called a “false delta sign” or pseudodelta sign
- Recommendation: avoid the confusion of the variations on “delta signs” and describe the findings
- Venous infarct: infarct that doesn’t follow arterial territories, especially near a dural sinus
- White matter edema
- Above changes occurring bilaterally
B, Transverse sinus thrombosis.
C, Straight sinus thrombosis.
D, Internal cerebral vein thrombosis (arrow) and left thalamic hypodensity (*).
E, Cord sign (arrow) and hyperdense sagittal sinus thrombosis (*).
F, Multiple small hemorrhages in same patient as in E. Arrows indicate cord sign.
IV contrast CT
- With contrast, the dura around the sinus may enhance and become denser than clot in 35% of cases.
- Near the Torcular herophili this produces what has been called the empty delta sign but sometimes this, too, is called the delta sign
- Gyral enhancement occurs in 32%
- Dense deep (white matter) veins (collateral flow)
- Intense tentorial enhancement (common)
CTV
- Good quality venogram is fastest available test but poor resolution for small cortical venous thromboses
MRI & MRA/MRV
- Gold standard recommended test by AHA and EFNS
- MRI excels for diagnosis and follow-up.
- MRI shows absence of flow and clot burden and demonstrates parenchymal changes including venous infarcts
- Can differentiate occluded sinus from congenital absence.
B: DWI showing venous infarct (blue arrowhead) adjacent to the thrombosed vein.
A, Bilateral thalamic hyperintensity (arrows) on fluid-attenuated inversion recovery (FLAIR) in a patient with deep cerebral vein thrombosis.
B, Susceptibility-weighted imaging shows hypointensity of the straight sinus (arrow), vein of Galen, and internal cerebral veins.
C, Venous infarction due to transverse sinus thrombosis with heterogeneous FLAIR hyperintensity (arrow).
D, Bilateral FLAIR hyperintensities (arrows) with mass effect in a patient with superior sagittal sinus thrombosis (arrow), shown in E on a contrast-enhanced T1 sequence and in F absent venous filling defect (arrow) with phase-contrast magnetic resonance venography.
- Shows cerebral oedema and non-acute haemorrhagic changes to better advantage than CT.
- Can help estimate age of clots
- MRI appearance of thrombosed sinuses at various stages
Age of clot in sinus | Hemoglobin state | T1WI appearance of clotted sinus | T2WI appearance of clotted sinus |
Acute (0–7 days) | Deoxyhemoglobin | Isointense | Hypointense (black): can mimic flow void |
Subacute | Methemoglobin | Hyperintense (1st) | Hyperintense (2nd) |
Late (recanalized) | Paramagnetic products of above | Black (flow void) | Black (flow void) |
- MR venography (MRV) tends to overestimate the degree of occlusion.
Catheter angiography for CVT
- Close to MRI in sensitivity
- Consider it to be the standard of diagnosis.
- MRI has some advantages over angiography
- On angiography a hypoplastic transverse sinus may not visualize,
- Non-opacified blood entering a sinus may mimic a filling defect).
- Be sure to image all the way to the venous phase (requires extra vigilance).
- Findings include:
- Non-filling of segments of sinuses, or filling defects in segments that are visualized
- Prolonged circulation time: present in 50% of cases (may need delayed films to see veins)
- Stumps and abnormal collateral pathways
LP
- LP is generally not indicated unless there is suspicion of meningitis.
- There are no specific CSF abnormalities, so LP is often not helpful.
- Opening pressure (OP) is increased in > 80%.
- CSF may be bloody or xanthochromic.
Bloodwork
- Routine bloods (CBC, chemistry, PT & aPTT)
- To detect prothrombotic conditions
- Protein C and S levels
- Antithrombin deficiency
- Antiphospholipid antibodies = anticardiolipin antibodies and lupus anticoagulant)
- Tests for specific predisposing conditions
- Factor II level,
- Serum homocysteine level,
- Paroxysmal nocturnal hemoglobinuria (PNH) panel,
- Leukocyte alkaline phosphatase.
- Tests for protein C & protein S, and antithrombin deficiency should be deferred until 2–4 weeks after completing anticoagulation
- Testing is of limited value on warfarin or in the acute setting since the acute process will cause numerous abnormalities in the clotting system
- D-dimer:
- A fibrin degradation product
- Sensitivity of 97.1%,
- Specificity of 91.2%
- Negative predictive value of 99.6%,
- Positive predictive value of 55.7%.
- A normal D-dimer level by a sensitive radioimmunoassay or ELISA may help identify patients with a low probability of CVT
- However, if suspicion is high, further evaluation is indicated.
Ultrasound
- May be used in diagnosis of superior sagittal sinus thrombosis in the neonate.
Management of CVT (adults)
- General information
- Principle:
- Treat the underlying abnormality (if possible).
- Management should be aggressive because recoverability of brain is probably greater than with arterial occlusive stroke.
- Management is challenging because measures that counteract thrombosis (e.g. anticoagulation) tend to increase the risk of hemorrhagic infarct (the risk of which is already increased), and measures that lower ICP tend to increase blood viscosity → increased coagulability.
- The following is derived from the
- 2011 AHA Scientific Statement for the Diagnosis and Management of Cerebral Venous Thrombosis and
- 2018 Report of the Society of NeuroInterventional Surgery on Endovascular Strategies for Cerebral Venous Thrombosis.
- Treatment specifics
- General measures
- Patients suspected of having infection should receive appropriate treatment:
- Antibiotics,
- Drainage of purulent collections…
- Seizures
- AED for a defined duration are recommended for a single seizure with or without parenchymal lesions to prevent further seizures
- AEDs are not recommended in the absence of seizures (potential harm)
- Steroids:
- Not recommended unless needed for other underlying disease (potential harm) (reduces fibrinolysis, increases coagulation)
- Control HTN
- Anticoagulation
- NICE: Offer people diagnosed with cerebral venous sinus thrombosis (including those with secondary cerebral haemorrhage) full-dose anticoagulation treatment (initially full-dose heparin and then warfarin [international normalised ratio 2 to 3]) unless there are comorbidities that preclude its use.
- Either
- DOAC (ACTION-CVT trial)
- Unfractionated heparin (UFW) or
- LMWH
- Numerous studies show a lower mortality rate with heparin than without.
- Best treatment even when there is evidence of intracerebral haemorrhage (ICH) with the attendant risk of increasing the size of the haemorrhage.
- No consensus on duration of treatment.
- Success rate may be higher if administered before patient becomes moribund
- During pregnancy, full dose LMWH is recommended over UFH
- Transition from heparin to vitamin K antagonists (e.g. warfarin)
- Monitor ICP if patient continues to deteriorate:
- Ventriculostomy is preferred, but use caution in placing catheter if patient is on heparin
- Hydrate aggressively as ICP tolerates
- Measures to lower ICP: differs somewhat from treatment for traumatic ICP elevation
- Acetazolamide (Level II55): one of the few measure to treat elevated ICP that does not rely on venous outflow
- Elevate HOB
- Drain CSF
- Pentobarbital coma: also does not depend on venous outflow
- Hyperosmotic and/or loop diuretics:
- Reserve for last
- Because diuretics → hypertonicity →↑ viscosity →↑ coagulation.
- Replace fluid loss with isotonic IV fluids to prevent dehydration; i.e., goal is hypertonic Euvolemia
- Monitor patients with increased ICP for progressive visual loss and treat elevated ICP urgently if detected.
- Treatment measures include: serial LPs, optic nerve sheath fenestration, or VP shunt
- Management of HCP
- VPS or LPS
- Optic nerve fenestration if there is localized oedema
- Endovascular therapy (EVT)
- For deterioration despite intensive anticoagulation (Level II55). There are no guidelines for how long to wait before declaring medical therapy a failure, decision takes into account how sick the patient is. Also, there is no information when to use DC vs. EVT. Modalities include chemical thrombolysis (direct injection of tPA into the sinus) and mechanical thrombectomy
- Decompressive craniectomy (DC):
- Indication: Neurologic deterioration due to mass effect or intracranial haemorrhage causing increased ICP.
- Risky, but may be lifesaving.
- Good prognostic indicators
- Early surgery (≤12 hrs from admission) AND
- Younger patients
- If DC is elected, the options of heparinization and tPA cannot be employed for ≈ 2–3 days
- Long-term anticoagulation after resolution of acute phase with heparin:
- Spontaneous CVT:
- Vitamin K antagonists (VKA) for 6–12 months
- Target INR=2–3
- CVT with risk factors that have been eliminated:
- VKA for 3–6 months,
- Target INR= 2–3
- Recurrent CVT, VTE after CVT, or severe thrombophilia (e.g. homozygous prothrombin G20210A, homozygous factor V Leiden, protein C or S or antithrombin deficiency, antiphospholipid syndrome, or combined thrombophilic conditions):
- Indefinite VKA,
- Target INR= 2–3
- Consider consultation with a physician with expertise in coagulation
- CVT during pregnancy:
- Continue full anticoagulation with LMWH during the pregnancy, and LMWH or VKA
- Target INR= 2–3 for ≥6 weeks post-partum (for a total duration of therapy of 6 months)
Management (paeds)
- Investigation
- CT imaging is fast and convenient, this modality may miss the diagnosis of CVST in up to 40% of cases,
- MRI with MR venogram (MRV) gold standard
- Treatment
- Primary treatment
- Anticoagulation with heparin.
- Additional therapies
- Thrombolysis or surgical thrombectomy
- Indicated when there is a failure to respond to anticoagulation.
- Associated with intracranial hemorrhage hence usually
Prognosis
- Morbidity & mortality:
- Natural history (without treatment):
- Mortality: 14–40% (based on small sample 82 sizes).
- With anticoagulation: ≈ 13% die or remain dependent.
- Poor prognosticators:
- Clinical status:
- Coma
- Rapid neurologic deterioration, focal signs
- Demographics
- Age:
- Extremes of age (infancy or elderly)
- Male gender
- Radiographic findings:
- Haemorrhages, especially larger hemorrhages
- Venous infarcts
- Deep venous involvement
- Future pregnancies in patients with a history of CVT
- Advise the patient that future pregnancy is not contraindicated.
- Consultation with a haematologist and/or maternal foetal medicine specialist is reasonable
- Prophylaxis with LMWH during future pregnancies and the post-partum period for women with a history of CVT is recommended
Differential diagnosis
- Idiopathic intracranial hypertension (pseudotumor cerebri)
- Arterial ischemic stroke
- Primary intracerebral hemorrhage
- Hemorrhagic stroke due to a vascular malformation
- Meningitis/encephalitis
- Brain abscess
- Systemic lupus erythematosus (by far the most common differential diagnosis, affecting mostly women as in cerebral venous thrombosis [CVT])
- Sarcoidosis (may have a presentation similar to CVT)
- Antiphospholipid syndrome (may have a presentation similar to CVT)
- Gliomatosis cerebri
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